• Title/Summary/Keyword: Nasopharyngeal carcinoma (NPC)

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Involvement of EBV-encoded BART-miRNAs and Dysregulated Cellular miRNAs in Nasopharyngeal Carcinoma Genesis

  • Xie, Yuan-Jie;Long, Zhi-Feng;He, Xiu-Sheng
    • Asian Pacific Journal of Cancer Prevention
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    • v.14 no.10
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    • pp.5637-5644
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    • 2013
  • The definite molecular mechanisms underlying the genesis of nasopharyngeal carcinomas (NPCs) remain to be completely elucidated. miRNAs are small non-coding RNAs which are implicated in cell proliferation, apoptosis, and even carcinogenesis through negatively regulating gene expression post-transcriptionally. EBV was the first human virus found to express miRNAs. EBV-encoded BART-miRNAs and dysregulated cellular miRNAs are involved in carcinogenesis of NPC by interfering in the expression of viral and host cell genes related to immune responses and perturbing signal pathways of proliferation, apoptosis, invasion, metastasis and even radio-chemo-therapy sensitivity. Additional studies on the roles of EBV-encoded miRNAs and cellular miRNAs will provide new insights concerning the complicated gene regulated network and shed light on novel strategies for the diagnosis, therapy and prognosis of NPC.

Clinical Factors Associated with Recurrence of Nasopharyngeal Carcinoma (비인두암의 재발에 연관된 임상적 지표)

  • Ok, Sohea;Lee, Soo-Hyung;Hwang, Sunjin;Park, Min-Woo;Cho, Jae-Gu;Baek, Seung-Kuk;Kwon, Soon-Young;Jung, Kwang-Yoon;Woo, Jeong-Soo
    • Korean Journal of Head & Neck Oncology
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    • v.30 no.1
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    • pp.5-9
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    • 2014
  • Background and Objectives : The objective of this study was to investigate clinical factors associated with recurrence of nasopharyngeal carcinoma(NPC). Materials and Methods : We performed a retrospective review of 112 diagnosed as nasopharyngeal carcinoma, treated concurrent chemo-radiotherapy(CCRT) and had complete response from March 1, 1995, to March 31, 2012. Results : Of the recurrent NPC patients, patients received 2nd line chemotherapy had more recurrence within 2 years(p=0.010). Especially, patients received 2nd line chemotherapy longer than 4 months tend to have recurrence early(p=0.035). Other factors are not different between recurrent and non-recurrent NPC patients. Conclusion : The presence and the duration of 2nd line chemotherapy are associated with early recurrence.

Dihydroaustrasulfone alcohol induces apoptosis in nasopharyngeal cancer cells by inducing reactive oxygen species-dependent inactivation of the PI3K/AKT pathway

  • Kok-Tong Tan;Yu-Hung Shih;Jiny Yin Gong;Xiang Zhang;Chiung-Yao Huang;Jui-Hsin Su;Jyh-Horng Sheu;Chi-Chen Lin
    • The Korean Journal of Physiology and Pharmacology
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    • v.27 no.4
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    • pp.383-398
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    • 2023
  • Dihydroaustrasulfone alcohol (DA), the synthetic precursor of a natural compound (austrasulfone) isolated from the coral species Cladiella australis, has shown cytotoxic effects against cancer cells. However, it is unknown whether DA has antitumor effects on nasopharyngeal carcinoma (NPC). In this study, we determined the antitumor effects of DA and investigated its mechanism of action on human NPC cells. The MTT assay was used to determine the cytotoxic effect of DA. Subsequently, apoptosis and reactive oxygen species (ROS) analyses were performed by using flow cytometry. Apoptotic and PI3K/AKT pathway-related protein expression was determined using Western blotting. We found that DA significantly reduced the viability of NPC-39 cells and determined that apoptosis was involved in DA-induced cell death. The activity of caspase-9, caspase-8, caspase-3, and PARP induced by DA suggested caspase-mediated apoptosis in DA-treated NPC-39 cells. Apoptosis-associated proteins (DR4, DR5, FAS) in extrinsic pathways were also elevated by DA. The enhanced expression of proapoptotic Bax and decreased expression of antiapoptotic BCL-2 suggested that DA mediated mitochondrial apoptosis. DA reduced the expression of pPI3K and p-AKT in NPC-39 cells. DA also reduced apoptosis after introducing an active AKT cDNA, indicating that DA could block the PI3K/AKT pathway from being activated. DA increased intracellular ROS, but N-acetylcysteine (NAC), a ROS scavenger, reduced DA-induced cytotoxicity. NAC also reversed the chances in pPI3K/AKT expression and reduced DA-induced apoptosis. These findings suggest that ROS-mediates DA-induced apoptosis and PI3K/AKT signaling inactivation in human NPC cells.

The Interleukin-18 Promoter -607C>A Polymorphism Contributes to Nasopharyngeal Carcinoma Risk: Evidence from a Meta-analysis Including 1,886 Subjects

  • Guo, Xu-Guang;Xia, Yong
    • Asian Pacific Journal of Cancer Prevention
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    • v.14 no.12
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    • pp.7577-7581
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    • 2013
  • The interleukin-18 promoter -607C>A gene polymorphism may be related to nasopharyngeal carcinoma (NPC) risk but the results of individual studies remain conflicting. A meta-analysis including 1,886 subjects from five individual studies was therefore performed to provide a more accurate estimation. Pooled odds ratios (ORs) and their corresponding 95% confidence intervals (95% CIs) were evaluated by fixed- or random-effects models. A significant relationship between interleukin-18 promoter -607C>A gene polymorphism and NPC was found in a dominant genetic model (OR: 1.351, 95% CI: 1.089-1.676, P=0.006, $P_{heterogeneity}$=0.904), a homozygote model (OR: 1.338, 95% CI: 1.023-1.751, P=0.034, $P_{heterogeneity}$=0.863), and a heterozygote model (OR: 1.357, 95% CI: 1.080-1.704, P=0.009, $P_{heterogeneity}$=0.824). No significant association was detected in either an allelic genetic model (OR: 1.077, 95% CI: 0.960-1.207, 0.207, $P_{heterogeneity}$=0.844) or a recessive genetic model (OR: 1.093, 95% CI: 0.878-1.361, P=0.425, $P_{heterogeneity}$=0.707). In conclusion, a significant association was found between interleukin-18 promoter -607C>A gene polymorphism and NPC risk. Individuals with the C allele of interleukin-18 promoter -607C>A gene polymorphism have a higher risk of NPC development.

Neck Node Bolus Technique in the Treatment of Nasopharyngeal Carcinoma with Intensity-modulated Radiotherapy

  • Phua, Chee Ee;Ung, Ngie Min;Tan, Boon Seang;Tan, Ai Lian;Eng, Kae Yann;Ng, Bong Seng
    • Asian Pacific Journal of Cancer Prevention
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    • v.13 no.12
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    • pp.6133-6137
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    • 2012
  • Purpose: To study the effect of bolus versus no bolus in the coverage of the nodal tumour volume with intensity-modulated radiotherapy (IMRT) for the treatment of nasopharyngeal carcinoma (NPC). Methods and Materials: This retrospective study used data from 5 consecutive patients with NPC who were treated with bolus for large neck nodes using IMRT from November 2011-January 2012 in our institute. All these patients were treated radically with IMRT according to our institution's protocol. Re-planning with IMRT without bolus for these patients with exactly the same target volumes were done for comparison. Comparison of the plans was done by comparing the V70 of PTV70-N, V66.5 of PTV70-N, V65.1 of PTV70-N and the surface dose of the PTV70-N. Results: The mean size of the largest diameter of the enlarged lymph nodes for the 5 patients was 3.9 cm. The mean distance of the GTV-N to the skin surface was 0.6 cm. The mean V70 of PTV70-N for the 5 patients showed an absolute advantage of 10.8% (92.4% vs. 81.6%) for the plan with bolus while the V66.5 of PTV70-N had an advantage of 8.1% (97.0% vs. 88.9%). The mean V65.1 also had an advantage of 7.1% (97.6% vs. 90.5%). The mean surface dose for the PTV70-N was also much higher at 61.1 Gy for the plans with bolus compared to only 23.5 Gy for the plans without bolus. Conclusion: Neck node bolus technique should be strongly considered in the treatment of NPC with enlarged lymph nodes treated with IMRT. It yields a superior dosimetry compared t o non-bolus plans with acceptable skin toxicity.

Intensity-Modulated Radiotherapy for Nasopharyngeal Carcinoma: Penang General Hospital Experience

  • Phua, Chee Ee;Tan, Boon Seang;Tan, Ai Lian;Eng, Kae Yann;Ng, Bong Seng;Malik, Rozita Abdul;Ishak, Wan Zamaniah Wan
    • Asian Pacific Journal of Cancer Prevention
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    • v.13 no.7
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    • pp.3287-3292
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    • 2012
  • Purpose: To study the overall treatment time (OTT) and acute toxicity of intensity-modulated radiotherapy (IMRT) treatment for nasopharyngeal carcinoma (NPC). Methods: This retrospective study covered all NPC patients who underwent radical IMRT treatment at the Penang General Hospital from June 2011 to February 2012. Patients of any age and stage of disease with histologically proven diagnosis were included. Information was collected on patient demographics, clinical stage, treatment received, including any neoadjuvant and/or concurrent chemotherapy, acute toxity and completion of IMRT within the OTT. Results: A total of 26 NPC patients were treated with IMRT during the study period; 88.5% had stage III/IV disease. 45.2% received neo-adjuvant chemotherapy while 50.0% were given concurrent chemo-irradiation. All patients completed the treatment and 92.3% within the 7 weeks OTT. Xerostomia was present in all patients with 92.3% having grade 2. Severe grade III/IV acute toxicity occurred in 73.1% of patients, the commonest of which was oral mucositis (57.6%). This was followed by dysphagia which occurred in 53.8%, skin reactions in 42.3% and weight loss in 19.2%. However, haematological toxicity was mild with only one patient having leucopaenia. Conclusion: IMRT treatment for NPC is feasible in our center. More importantly, it can be delivered within the 7 weeks OTT in the majority of patients. Severe grade 3/4 toxicity is very common (73.1%) and thus maximal nutritional and analgesic support is required throughout the treatment.

Systematic Review on Epstein-Barr Virus (EBV) DNA in Diagnosis of Nasopharyngeal Carcinoma in Asian Populations

  • Han, Bao-Lin;Xu, Xiang-Ying;Zhang, Chun-Zhi;Wu, Jian-Juan;Han, Chun-Feng;Wang, Hui;Wang, Xuan;Wang, Guang-Shun;Yang, Shu-Juan;Xie, Yao
    • Asian Pacific Journal of Cancer Prevention
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    • v.13 no.6
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    • pp.2577-2581
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    • 2012
  • Objective: To conduct a meta-analysis to investigate the value of EBV DNA in diagnosis of nasopharyngeal cancer (NPC) in Asian populations, and provide important evidence for screening. Methods: Prospective or respective case-control or cohort studies regarding the detection role of EBV DNA for NPC were included in our study. We conducted a comprehensive literature search in PubMed, EMBASE, and the Chinese Biomedical Database (CBM database between January 1980 and March 2012. Results: A total of 18 studies with 1492 NPC cases and 2641 health controls were included. Almost of the included studies were conducted in China, and only one other conducted in Thailand. The overall results demonstrated that the pooled sensitivity, specificity, positive likelihood (+LR) and negative likelihood (-LR) were 0.73 (0.71-0.75), 0.89 (0.88-0.90), 8.84 (5.65-13.84) and 0.19(0.11-0.32), respectively. The overall EBV DNA detection showed the largest area of 0.932 under the summary receiver operator curve (SROC). The accuracy of detection by plasma for NPC (0.86) was higher than in serum (0.81), with largest areas under the SROC of 0.97 and 0.91, respectively. Conclusion: Our results demonstrated the EBV DNA detection in plasma or serum has high sensitivity and specificity in diagnosis of NPC, especially in Chinese populations with a high risk of cancer.

Association Between GSTM1 Polymorphism and Nasopharyngeal Cancer Susceptibility: a Meta-analysis

  • Sun, Zhen-Feng;Zhang, Jia;Xu, Hong-Ming;Wang, Guo-Liang;Dong, Pin
    • Asian Pacific Journal of Cancer Prevention
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    • v.13 no.11
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    • pp.5817-5821
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    • 2012
  • Background/Aims: Glutathione S-transferase M1 (GSTM1) is a multifunctional enzyme that plays a critical role in the detoxification of varieties of carcinogenic metabolites. Many studies have been conducted to investigate the association between GSTM1 polymorphism and nasopharyngeal cancer (NPC) risk, but the findings among those studies are inconsistent. To assess this relationship more precisely, we performed a meta-analysis of all available studies on the subject. Methods: Case-control studies were identified by searching Pubmed, Embase, ISI Web of Science, and Wanfang databases through September 6, 2012. We used the pooled odds ratio (OR) with its corresponding 95% confidence interval (95%CI) to evaluate the association of GSTM1 polymorphism with NPC susceptibility. Subgroup analyses by pathological types, sex and smoking status were performed to further identify the association. Results: Overall, 11 published studies with 1,513 cases and 2,802 controls were finally included into this meta-analysis according to the inclusion criteria. Meta-analysis of total studies showed that the null genotype of GSTM1 was significantly associated with increased risk of NPC, when comparing with the non-null genotype (OR=1.51, 95%CI=1.33-1.72, POR<0.001). The association was still statistically significant in subgroup analysis of patients with nasopharyngeal squamous cell carcinoma (OR=1.73, 95%CI=1.24-2.42, POR=0.001). Males with the null genotype of GSTM1 were more likely to subject to NPC than females. In addition, the association between the null genotype of GSTM1 and NPC risk was strongest in individuals with exposure to smoking. Sensitivity analysis by sequential omission of any individual studies one at a time further demonstrated the significant association. Conclusions: The findings suggest that the null genotype of GSTM1 is a risk factor for NPC, and there is a gene-smoking interaction in this association.

Comparison of Treatment Compliance and Nutritional Outcomes among Patients with Nasopharyngeal Carcinoma with and without Percutaneous Endoscopic Gastrostomy during Chemoradiation

  • Peerawong, Thanarpan;Phungrassami, Temsak;Pruegsanusak, Kovit;Sangthong, Rassamee
    • Asian Pacific Journal of Cancer Prevention
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    • v.13 no.11
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    • pp.5805-5809
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    • 2012
  • Aims: The study aimed to compare treatment compliance and nutritional outcomes in nasopharyngeal carcinoma (NPC) patients during chemoradiation. Methods: Clinical information of patients with NPC that underwent chemoradiation during 2004-2009 were retrieved from the hospital database and retrospectively reviewed. Patients were categorised into a prophylactic percutaneous endoscopic gastrostomy (PPEG) group and a non-PPEG group. Clinical information including treatment compliance, weight, haematological and renal toxicity was compared. Results: A total of 219 patients were reviewed and categorised into PPEG (n=77) and non-PPEG (n=142). Significant differences in absolute percentage weight loss between groups were found from the $3^{rd}$ cycle of chemotherapy. There were 24.2, 20.3 and 24.8% in the third, the fourth and the fifth cycles of chemotherapy, respectively. Migration of grade 2 to grade 3 weight loss was obviously seen in the $3^{rd}$ cycle as well. A significant difference of grade 3 or more hypokalemia was found with values of 14.3% and 50% in the PPEG and non-PPEG groups, respectively. Other toxicity parameters and treatment compliance were not different between the groups. Conclusions: Use of PPEG resulted in decreased severe weight loss, reduced migration from grade 2 to grade 3 weight loss and reduced hypokalaemia. However, benefits in treatment compliance could not be detected. So consideration of PPEG in NPC patients requires care.